This laboratory is primarily interested in the regulation of purine biosynthesis de novo in man. Studies are being conducted on three levels: 1) patients with inherited or acquired disorders of purine metabolism are being evaluated on the Clinical Research Unit for the pathogenesis of their hyperuricemia 2) control of purine biosynthesis de novo is being studied in human fibroblasts, lymphoblasts and hepatocytes grown in tissue culture 3) PP-ribose-P amidotransferase, the first enzyme in the de novo pathway, is being purified and its kinetic properties characterized. The above studies are designed to determine the importance of PP-ribose-P, purine ribonucleotide, glutamine and ammonia concentrations in the control of purine biosynthesis de novo. Relationships between purine overproduction and obesity, hyperlipidemia, ethanol ingestion and protein intake are also being evaluated.